Study Notes on Hemoglobin

Hemoglobin Overview

Definitions and Adaptations

  • Hemoglobin AHL B3.1.11: Adaptations of fetal and adult hemoglobin for the transport of oxygen.

  • Hemoglobin AHL B3.1.13: Oxygen dissociation curves as a means of representing the affinity of hemoglobin for oxygen at different oxygen concentrations.

Hemoglobin Function

  • Definition: Hemoglobin is a protein found in red blood cells that binds to oxygen in the lungs and transports it to tissues and organs throughout the body.

  • Spelling Variants:

    • American English: Hemoglobin

    • British English: Haemoglobin

  • Correctness: Both spellings refer to the same substance and are deemed correct.

Hemoglobin Structure

Conjugated Protein

  • Hemoglobin is classified as a conjugated protein:

    • Contains both a polypeptide chain (protein portion) and a prosthetic group (non-protein portion).

Protein Portion

  • The protein portion of hemoglobin is referred to as globin, composed of:

    • Alpha (α) chains

    • Beta (β) chains

  • Hemoglobin is a quaternary protein, meaning it consists of multiple polypeptide chains forming a functional molecule.

  • Total polypeptide subunits: Four

Non-Protein Portion

  • The non-protein portion of hemoglobin is called haem:

    • Each of the four polypeptide subunits is associated with a haem group.

    • Haem Group Composition: Contains a central iron ion (Fe²⁺), responsible for oxygen binding.

  • Each hemoglobin molecule can bind to a total of four molecules of oxygen (O₂).

Affinity

  • Definition: In biology, "affinity" pertains to the strength of the interaction or binding between two molecules.

    • High Affinity: Strong attraction leads to tight binding.

    • Low Affinity: Weak attraction leads to easy dissociation (break apart).

  • Oxygen Dissociation Curves:

    • Graphs that represent the affinity of hemoglobin for oxygen at different oxygen concentrations.

  • Conformational Change: When oxygen binds to hemoglobin, a shape change occurs, altering hemoglobin's affinity for oxygen.

Oxygen Dissociation Curve

Graph Representation

  • X-axis: Represents the partial pressure of oxygen (pO₂), a measure of oxygen concentration.

  • Y-axis: Represents the percentage saturation of hemoglobin with oxygen, indicating the proportion of hemoglobin molecules carrying oxygen.

Sigmoid Shape

  • The curve is sigmoid, indicating cooperative binding.

    • This shape occurs instead of a linear relationship due to increasing affinity for oxygen as more O₂ binds (2nd, 3rd, and 4th O₂).

Cooperative Binding of Oxygen

Reversible Binding

  • Oxygen binds reversibly to hemoglobin:

    • When no oxygen is bound, hemoglobin is termed deoxyhemoglobin.

    • When oxygen is bound, it is known as oxyhemoglobin.

Binding Dynamics

  • Binding of O₂ results in a conformational change:

    • When the first oxygen binds to a haem group, the other haem groups' affinities for O₂ increase, leading to rapid binding of the subsequent three O₂.

    • Ensures fast oxygen uptake in high oxygen environments (e.g., alveoli).

Release Dynamics

  • Conversely, the release of O₂ from one haem group results in a change that reduces the affinity of other haem groups for O₂:

    • When one oxygen is released, the other three quickly follow.

    • Ensures efficient delivery of oxygen in low oxygen environments (tissues).

Hemoglobin Interaction with O₂

At the Alveoli

  • Affinity: High affinity for oxygen due to high surrounding O₂ concentration.

  • Result: Hemoglobin binds to O₂ and becomes saturated in the lung alveoli capillaries.

At the Body Tissues

  • Affinity: Low affinity for oxygen due to lower surrounding O₂ concentration.

  • Result: Hemoglobin releases O₂ and becomes unsaturated in body tissue capillaries.

Fetal Hemoglobin

Differentiation Pre- and Post-Birth

  • Humans produce different forms of hemoglobin before and after birth.

  • Fetal Hemoglobin Composition: Two alpha and two gamma polypeptide subunits.

  • Adult Hemoglobin Composition: Two alpha and two beta polypeptide subunits.

Affinity Comparison

  • Strength of Affinity: Fetal hemoglobin has a stronger affinity for oxygen compared to adult hemoglobin.

  • Importance: This adaptation allows the fetus to effectively extract oxygen from the mother's blood via the placenta.

  • Mechanism: Oxygen is released from maternal hemoglobin in the placenta, diffuses into fetal circulation, then is transported by fetal hemoglobin to developing tissues.

Frequently Asked Questions (FAQ)

FAQ 1: Need for Hemoglobin

  • Hemoglobin is essential because while oxygen can dissolve in blood plasma, only small amounts can be transported that way.

  • Hemoglobin increases the oxygen-carrying capacity of blood dramatically (about 70 times more than plasma alone).

  • Without hemoglobin, adequate oxygen delivery to tissues would not be possible.

FAQ 2: Dissociation Graph Shape

  • The oxygen dissociation graph is not a straight line because binding is cooperative:

    • The first oxygen binds with difficulty, while subsequent oxygens bind more easily.

  • The sigmoid (S-shaped) curve arises from this changing affinity contrary to a straight line which would indicate a constant affinity.

FAQ 3: First Oxygen Binding Difficulty

  • The first binding is more difficult because deoxyhemoglobin starts in a “low-affinity” shape.

  • When the first O₂ binds, conformational changes allow the next oxygen molecules to bind more easily.

FAQ 4: Mechanism of Conformational Change

  • Hemoglobin does not actively 'know' to change shape; it is a result of chemical and physical processes.

  • The binding of O₂ to iron alters internals forces, leading to structural adjustments of the protein.

FAQ 5: Definition of Partial Pressure of Oxygen (pO₂)

  • Definition: A measure of available oxygen in a gas mixture.

    • Higher pO₂ indicates more oxygen; lower pO₂ indicates less oxygen.

  • Oxygen dissociation curve effectiveness is analyzed across varying pO₂ levels.

FAQ 6: Affinity Variation in Lungs and Tissues

  • Affinity for oxygen is influenced by surrounding concentration:

    • In the lungs: High concentration results in high affinity, leading to oxygen binding.

    • In body tissues: Low concentration leads to decreased affinity and oxygen release.

FAQ 7: Release of Oxygen Mechanism

  • Cooperativity aids in oxygen release:

    • The exit of the first oxygen prompts hemoglobin to revert toward its low-affinity shape, easing subsequent oxygen release.

FAQ 8: Structure of Fetal Hemoglobin

  • Fetal hemoglobin features gamma chains, which impart a slightly different shape.

  • This structural difference enhances fetal hemoglobin's affinity for oxygen, crucial for oxygen acquisition from maternal blood at the placenta.

FAQ 9: Oxygen Transfer Dynamics

  • The mother does not experience oxygen deprivation; oxygen transfer is controlled and replenished continuously via normal breathing.

FAQ 10: Transition from Fetal to Adult Hemoglobin

  • Timing of Switch:

    • Begins shortly before birth; continues during early months of life.

    • By approximately 6 months of age, most hemoglobin in circulation transitions to the adult form.